Intrauterine growth restriction is associated with alterations in placental lipoprotein receptors and maternal lipoprotein composition

Among other factors, fetal growth requires maternal supply of cholesterol.
Cellular cholesterol uptake is mainly mediated by the LDL receptor
(LDL-R) and the scavenger receptor family. We hypothesized that
expression levels of key receptors of these families were regulated
differently in placentas from IUGR pregnancies with varying degrees
of severity. Third-trimester placentas from IUGR pregnancies with
(IUGR-S) and without (IUGR-M) fetal hemodynamic changes and
from control (AGA) pregnancies were studied. LDL-R, LDL-Rrelated
protein (LRP-1), and scavenger receptor class B type I (SR-BI)
mRNA and protein levels were measured. Cholesterol concentration
and composition of lipoproteins were analyzed enzymatically and by
lipid electrophoresis, respectively, in maternal and umbilical cord
blood. LDL-R mRNA levels in IUGR-M were similar to AGA but
lower (P ! 0.05) in IUGR-S. In contrast, LDL-R protein was twofold
(IUGR-M) and 1.8-fold (IUGR-S) higher (P ! 0.05) than in the AGA
group. LRP-1 mRNA and protein levels were not altered in the IUGR
cases. SR-BI mRNA was unchanged in IUGR, but protein levels were
lower (P ! 0.05) in IUGR-S than in the other groups. Maternal
plasma concentrations of LDL cholesterol were higher (P ! 0.05) in
the AGA group (188.5 " 23.6 mg/dl) than in the IUGR-S group
(154.2 " 26.1). Electrophoretic mobility of the LDL fraction in
maternal plasma demonstrated significant changes in migration toward
higher values (AGA 0.95 " 0.06, IUGR-M 1.12 " 0.11, P !
0.001; IUGR-S 1.28 " 0.20, P # 0.002). We conclude that LDL-R
and SR-BI levels are altered in IUGR pregnancies. These differences
were associated with changes in LDL, but not HDL, mobility and cholesterol concentration in maternal circulation.